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PXD055878

PXD055878 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe SIRT1 activating compound SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery
DescriptionDuchenne muscular dystrophy (DMD) is a rare and devastating genetic disorder, whose management is still a major challenge, despite progress in genetic and pharmacological disease-modifying treatments have been made. Mitochondrial dysfunctions contribute to DMD, however, there are no effective mitochondrial therapies for DMD. SIRT1 is a NAD+-dependent class III histone deacetylase that controls several key processes and whose impairment is involved in determining mitochondrial dysfunction in DMD. In addition to well-known resveratrol, other potent selective activators of SIRT1 exist, with better pharmacokinetics properties. Among these, SRT2104 is the most promising and advanced in clinical studies. Here we unveil the beneficial effects of SRT2104 in flies, mice, and patient-derived myoblasts as different models of DMD, demonstrating an anti-inflammatory, anti-fibrotic, and pro-regenerative action of the drug. We also elucidate, by molecular dynamics simulations, that a conformational selection mechanism is responsible for the activation of SIRT1. Further, the impact of SRT2104 in reshaping muscle proteome and acetylome profiles has been investigated, highlighting the drug as an attractive exercise mimetic for the treatment of DMD. Overall, our data suggest SRT2104 as a possible therapeutic candidate to successfully counteract the progression of the dystrophic phenotype in DMD.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-07_02:54:26.082.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD055878
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterErica Gianazza
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-16 01:18:21ID requested
12025-05-07 02:54:26announced
Publication List
10.1038/s41419-025-07595-z;
Giovarelli M, Zecchini S, Casati SR, Lociuro L, Gjana O, Mollica L, Pisanu E, Mbissam HD, Cappellari O, De Santis C, Arcari A, Bigot A, Clerici G, Catalani E, Del Quondam S, Andolfo A, Braccia C, Cattaneo MG, Banfi C, Brunetti D, Mocciaro E, De Luca A, Clementi E, Cervia D, Perrotta C, De Palma C, The SIRT1 activator SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery. Cell Death Dis, 16(1):259(2025) [pubmed]
10.6019/PXD055878;
Keyword List
submitter keyword: metabolism,muscular dystrophy, SIRT1, mitochondria
Contact List
Clara De Palma
contact affiliationDept of Medical Biotechnology and Translational Medicine,University of Milan, Milan
contact emailclara.depalma@unimi.it
lab head
Erica Gianazza
contact affiliationCentro Cardiologico Monzino
contact emailerica.gianazza@cardiologicomonzino.it
dataset submitter
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Dataset FTP location
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PRIDE project URI
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